Laboratory Studies

No laboratory studies have been universally accepted for the diagnosis and treatment of infantile hemangiomas; however, reports in the literature have investigated the use of serum vascular endothelial growth factor (VEGF) as well as urinary beta-fibroblast growth factor, VEGF, and matrix metalloproteinases (MMPs) as markers of hemangioma proliferation and differentiation.
[5, 6]

Use of glucose transporter 1 (GLUT-1) stain is helpful for evaluating tissue removed during biopsy or excision.
[60] Both proliferating and involuting infantile hemangiomas uniformly stain positively for GLUT-1, while other cutaneous vascular neoplasms, malformations, and normal cutaneous vasculature do not, making this stain very sensitive and specific for histologic confirmation of infantile hemangiomas. In addition, red blood cell membranes stain positively for GLUT-1, creating an effective internal control.

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Imaging Studies

MRI with and without intravenous gadolinium is the imaging modality of choice to delineate the location and extent of both cutaneous and extracutaneous hemangiomas. MRI also helps in differentiating other high-flow vascular lesions (eg, arteriovenous malformations vs proliferating hemangiomas). Involuting hemangiomas have features that resemble low-flow lesions (eg, venous malformations).

Ultrasonography is useful in differentiating hemangiomas from other deep dermal or subcutaneous structures, such as cysts, pilomatrixomas, or lymph nodes. Ultrasonography is generally limited by its inability to fully evaluate the magnitude and extent of the hemangioma. Dubois et al found that an evaluation exhibiting high vessel density (>5 vessels/cm2) and high peak arterial Doppler shift (>2 kHz) was both sensitive and specific for infantile hemangiomas compared with other soft-tissue masses.
[7]

Plain radiography is fairly limited but may be useful for evaluating hemangiomas that impinge on the airway.

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Procedures

If the diagnosis is in question after a thorough history and physical examination, a skin biopsy can be helpful in distinguishing unusual or atypical hemangiomas from other vascular lesions. Specimens may be evaluated by routine histological examination and special stains as outlined in Histologic Findings.

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Histologic Findings

Routine histopathology varies according to the stage of the hemangioma. In early proliferation, hemangiomas are characterized by nonencapsulated masses and dense cords of mitotically active, plump endothelial cells in close association with pericytes. Few, small caliber lumina are present. Special stains reveal well-developed basement membranes around primitive vessels. Mast cells are present in varying numbers in all stages. As the hemangioma proliferates, the vascular lumina enlarge. An increase of apoptotic endothelial cells and a decrease in plump, mitotically active endothelial cells herald the involution phase.

As involution progresses, the endothelial cells continue to mature and assume a flatter appearance. The vascular lumina continue to enlarge until few, mature ectatic vessels remain.
[61] The proliferating endothelial cell mass may be replaced with fibrofatty tissue. Varying degrees of epidermal atrophy, scar tissue, and loss of elastic tissue can be seen in late involuting lesions.
[62]

Specimens may be evaluated for tissue-specific immunohistochemical markers such as GLUT-1, merosin, Fc-gamma-RII, and Lewis Y antigens. These markers may aid in differentiating infantile hemangiomas (positive staining for all) from other vascular neoplasms or malformations, such as the congenital hemangiomas (eg, rapidly involuting congenital hemangioma, noninvoluting congenital hemangioma, partially involuting congenital hemangioma), kaposiform hemangioendothelioma, tufted angioma, or pyogenic granuloma, none of which stains positively for these antigens. These markers are coexpressed by infantile hemangiomas, erythrocyte cell membranes, and placental microvessels.
[60]

Histopathology of a proliferating infantile hemangioma with plump endothelial cells in the dermis.

This proliferating superficial infantile hemangioma on the trunk required no therapy.

Exquisitely painful ulcerated mixed hemangioma (superficial and deep) of the left deltoid in a 6-month-old female infant. This lesion was treated successfully with pulsed dye laser.

This superficial and deep infantile hemangioma resulted in astigmatism of the left eye, requiring spectacles to correct the refractive error and to prevent amblyopia. Further growth of this hemangioma necessitated a course of oral prednisolone. The hemangioma shrunk rapidly, and the patient's astigmatism decreased such that the spectacles were unnecessary 1 month after beginning steroids.

Segmental infantile hemangioma in a female infant with PHACE syndrome involving the posterior neck and right forehead associated with an absent right vertebral artery and a laryngeal hemangioma.

Segmental infantile hemangioma with minimal or arrested growth of the bilateral buttocks and posterior thigh in this male infant with PELVIS syndrome (complicated by cutaneous ulceration, hypospadias, anal stenosis, intraspinal lipoma with tethered cord). The white material is a barrier diaper cream.